Humans have been reported to have an age-dependent sensitivity to the amnesic and central nervous (CNS) depressant effects of diazepam. Evidence is presented in this proposal showing that diazepam elicits an age-dependent impairment of the passive-avoidance response in the rat. The objectives of the proposed research are to determine in the rat: (1) whether the number of binding sites and/or the binding site affinity of (3H) diazepam changes with age in various areas of the brain, (2) the effect of age on the pharmacokinetics of diazepam and its metabolites, (3) whether the male rat has an age-dependent sensitivity to the CNS depressant effect, antianxiety effect, and the learning and/or memory impairment produced by diazepam, (4) whether the age-dependent behavioral effects of diazepam are due to age-related changes in the kinetics and/or receptor binding of diazepam and (5) the role of diazepam's metabolites in the age-dependent reduction of the passive-avoidance response seen with diazepam. Young, mature and old adult male Fischer 344 rats will be used as the experimental subjects. The sensitivity of rats in each of the three age groups to the amnesic effects of diazepam will be measured by a sequential, matching-to-sample task. The choice escape learning test will be used to determine the impairment of learning and/or performance produced by diazepam. A conflict test will be used to measure the sensitivity of the rats to the CNS depressant and antianxiety effect of diazepam. Multiple regression will be used to establish whether correlations exist among age-related behavioral effects of diazepam and changes in receptor binding and/or kinetics of diazepam. The role of diazepam's metabolites in the age-dependent impairment of the passive-avoidance task seen with diazepam will be resolved by: (1) measuring the ability of each metabolite to inhibit the passive-avoidance response and (2) determining whether the blood levels of the metabolite(s) are high enough to impair the passive-avoidance response after an injection of diazepam.